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Neurobiological Correlates of Susceptibility, Resilience, and Recovery to Substance Abuse in Participants with Childhood Maltreatment

Award Number: R01DA065290
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2031

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Neurobiological Correlates of Susceptibility, Resilience, and Recovery to Substance Abuse in Participants with Childhood Maltreatment - PROJECT SUMMARY Childhood adversity is a critical risk factor for substance use disorders (SUDs), yet substantial numbers of exposed individuals remain resilient. Understanding neurobiological mechanisms underlying resilience may provide insights for prevention and intervention. Using diffusion tensor imaging and structural connectome analysis, we identified nine brain network nodes where reduced nodal efficiency distinguished resilient from susceptible young adults with comparable childhood maltreatment, achieving ~80% cross-validated classification accuracy. These findings suggest resilient individuals are not unaffected but effectively compensated through specific network adaptations. This proposal validates and extends these findings in the Adolescent Brain Cognitive Development (ABCD) Study, the largest longitudinal neuroimaging study of adolescent development (N~11,000). We employ an exposome-wide association study (ExWAS) approach to identify high-risk youth based on comprehensive multi-domain adversity burden. Growth mixture modeling will identify substance use trajectories, classifying participants as resilient (high adversity, low substance use), susceptible (high adversity, escalating use), or low-risk controls. Three aims will: (1) Validate our resilience network model using modern tractography and higher-resolution parcellations, testing whether network features distinguish resilient from susceptible adolescents despite equivalent exposome burden and examining disorder-specific versus transdiagnostic mechanisms; (2) Distinguish constitutional resilience (protective features present at baseline, ages 9-10) from acquired resilience (progressive node recruitment across adolescence), revealing whether resilience is fixed or modifiable; (3) Identify modifiable protective factors (family support, school engagement, peer relationships, activities) associating with resilient architecture and preceding node recruitment, using machine learning to determine which factors at which ages most strongly promote resilience. Exploratory analyses test whether sleep disruption mediates network effects on substance use, building on our finding that sleep efficiency mediated 39-46% of maltreatment effects on brain structure. We hypothesize that sleep degradation emerges 12-18 months before substance use escalation, providing an intervention window. This research establishes whether network architecture represents a robust biomarker of SUD resilience; reveals modifiable environmental targets and critical developmental windows; and distinguishes constitutional from acquired resilience to inform precision prevention. Identifying naturally-occurring protective brain adaptations and fostering experiences transforms resilience from abstract construct into actionable prevention targets for high-risk youth.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $981,978 )
2026	2026	THE MCLEAN HOSPITAL CORPORATION	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	1	9/3/2026	NEW	$981,978
														Subtotal = $981,978

Grand Total All Awards = $981,978

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Neurobiological Correlates of Susceptibility, Resilience, and Recovery to Substance Abuse in Participants with Childhood Maltreatment

Award Number: R01DA065290

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/15/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2031

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